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Adjuvant treatment for pancreatic cancer.

ABSTRACT: Pancreatic cancer is the third leading cause of cancer-associated mortality in Western countries. Upfront resection with adjuvant chemotherapy is the treatment of choice in resectable tumors, offering the chance for cure. Until the 1990s, adjuvant therapy was not routinely used after resection for pancreatic cancer. During the last three decades however, enormous progress has been made in evidence-based onco-surgical management of resectable pancreatic cancer. Based on the results from multicenter randomized controlled trials, primarily initiated by the European Study Group of Pancreatic Cancer (ESPAC), adjuvant chemotherapy has become the gold standard after upfront resection, while adjuvant chemoradiotherapy is not recommended. Combination chemotherapy with gemcitabine and capecitabine was shown to significantly prolong median overall survival after resection compared to monotherapy with either gemcitabine or 5-fluorouracil/folinic acid. Recent data from the French-Canadian Uni-Cancer GI PRODIGE 24/CCTG PA.6 trial showed that adjuvant poly-agent chemotherapy with modified FOLFIRINOX achieved median survival times of 54.4 months in selected patients. Despite improved survival times after resection followed by adjuvant chemotherapy, however, recurrence occurs still in more than 75% of patients within the first 2 years after resection. Further efforts are therefore to be made in early detection tools, the evaluation of neoadjuvant strategies, the development of new drug targets, and stratification strategies to better select patients for the available therapies. This review article summarizes the body of evidence on adjuvant treatment for pancreatic cancer, identifies evidence gaps and provides future perspectives.

SUBMITTER: Klaiber U

PROVIDER: S-EPMC6509427 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Adjuvant treatment for pancreatic cancer.

Klaiber Ulla U Hackert Thilo T Neoptolemos John P JP

Translational gastroenterology and hepatology 20190429

Pancreatic cancer is the third leading cause of cancer-associated mortality in Western countries. Upfront resection with adjuvant chemotherapy is the treatment of choice in resectable tumors, offering the chance for cure. Until the 1990s, adjuvant therapy was not routinely used after resection for pancreatic cancer. During the last three decades however, enormous progress has been made in evidence-based onco-surgical management of resectable pancreatic cancer. Based on the results from multicent ...[more]

PMID: 31143848

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Project description:ImportanceThe benefit of adjuvant chemotherapy after resection of pancreatic cancer following neoadjuvant combination treatment with folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) is unclear.ObjectiveTo assess the association of adjuvant chemotherapy with overall survival (OS) in patients after pancreatic cancer resection and neoadjuvant FOLFIRINOX treatment.Design, setting, and participantsThis international, multicenter, retrospective cohort study was conducted from January 1, 2012, to December 31, 2018. An existing cohort of patients undergoing resection of pancreatic cancer after FOLFIRINOX was updated and expanded for the purpose of this study. All consecutive patients who underwent pancreatic surgery after at least 2 cycles of neoadjuvant FOLFIRINOX chemotherapy for nonmetastatic pancreatic cancer were retrospectively identified from institutional databases. Patients with resectable pancreatic cancer, borderline resectable pancreatic cancer, and locally advanced pancreatic cancer were eligible for this study. Patients with in-hospital mortality or who died within 3 months after surgery were excluded.ExposuresThe association of adjuvant chemotherapy with OS was evaluated in different subgroups including interaction terms for clinicopathological parameters with adjuvant treatment in a multivariable Cox model. Overall survival was defined as the time starting from surgery plus 3 months (moment eligible for adjuvant therapy), unless mentioned otherwise.ResultsWe included 520 patients (median [interquartile range] age, 61 [53-66] years; 279 [53.7%] men) from 31 centers in 19 countries. The median number of neoadjuvant cycles of FOLFIRINOX was 6 (interquartile range, 5-8). Overall, 343 patients (66.0%) received adjuvant chemotherapy, of whom 68 (19.8%) received FOLFIRINOX, 201 (58.6%) received gemcitabine-based chemotherapy, 14 (4.1%) received capecitabine, 45 (13.1%) received a combination or other agents, and 15 (4.4%) received an unknown type of adjuvant chemotherapy. Median OS was 38 months (95% CI, 36-46 months) after diagnosis and 31 months (95% CI, 29-37 months) after surgery. No survival difference was found for patients who received adjuvant chemotherapy vs those who did not (median OS, 29 vs 29 months, univariable hazard ratio [HR], 0.99; 95% CI, 0.77-1.28; P = .93). In multivariable analysis, only the interaction term for lymph node stage with adjuvant therapy was statistically significant: In patients with pathology-proven node-positive disease, adjuvant chemotherapy was associated with improved survival (median OS, 26 vs 13 months; multivariable HR, 0.41 [95% CI, 0.22-0.75]; P = .004). In patients with node-negative disease, adjuvant chemotherapy was not associated with improved survival (median OS, 38 vs 54 months; multivariable HR, 0.85; 95% CI, 0.35-2.10; P = .73).Conclusions and relevanceThese results suggest that adjuvant chemotherapy after neoadjuvant FOLFIRINOX and resection of pancreatic cancer was associated with improved survival only in patients with pathology-proven node-positive disease. Future randomized studies should be conducted to confirm this finding.

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Adjuvant treatment for pancreatic cancer.

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Adjuvant treatment for pancreatic cancer.

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